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Dermal Fillers: Ever-Expanding Options For Esthetic Use

M. J. A. Sapijaszko, MD, FRCPC
Department of Medicine, Division of Dermatology, University of Alberta, Edmonton, AB, Canada

ABSTRACT

Aesthetic volume rejuvenation with dermal fillers continues to be a very popular procedure that is sought by a growing number of patients who seek the rounder softer contours attributable to a more youthful appearance, including fuller curves of the cheeks, lips, and temples. Not only are fillers easier to use, but the outcomes that equal or exceed more invasive surgical options make volume restoration an increasingly popular procedure. Continued patient demand has fueled the introduction of a wider variety of injectable fillers, which include dermal and subdermal fillers with varying degrees of viscosity and duration of benefit. There are also several dermal implants that have stood the test of time or offer innovative technologies and approaches. This article will focus on the most popular, time-tested, and innovative fillers available today.

Key Words: Dermal fillers, facial rejuvenation, lip augmentation

The advances in medical care and improvements in patients’ quality of life have resulted in an increasing movement from practicing medicine for disease detection and treatment, to the prevention and alleviation of the inevitable signs of ageing. The youthful fullness and curves of the face are altered and reduced as we age. One of the features of the ageing face is the loss and redistribution of facial fat and collagen. These changes, in combination with static and dynamic facial rhytids, are largely responsible for the emergence and expansion of corrective surgery. There is a trend toward less invasive approaches. Different modalities are used to address each aspect of facial ageing. In most cases, these techniques work synergistically to deliver the desired results, and in that regard, facial volume augmentation can be considered as one of the most important components of a comprehensive facial rejuvenation program.

Recent advances in soft tissue augmentation materials, techniques, and approaches have greatly increased the therapeutic options available to our patients. With proper techniques and skills, these products can restore the facial youthfulness with relative ease and little or no downtime for patient recovery. The following discussion will focus on the most popular dermal and subdermal fillers that have stood the test of time, as well as those that offer innovative advances and approaches.

Autologous Fat

Autologous fat continues to be one of the more popular dermal fillers because it is fully biocompatible, allowing for transferability from one area of the body to another in the same patient. It is also biodegradable and plentiful. The degree of permanency of autologous fat in the recipient site varies depending on the technique used by the physician, as well as patient factors. Influencing factors such as smoking habits and anticoagulation (both exert a negative effect on fat graft survival), as well as physician care, and meticulous attention to detail (both can enhance the effect on fat graft survival) are important predictors of procedural and outcome success. With the abundance of supply, larger volumes can be injected/ transferred without significantly adding cost to the patient. The objective of the procedure is to produce a high rate of fat graft uptake by optimizing conditions for survivability of cells at recipient sites, such as the cheeks, lips, temples, as well as the back of the hands.

Recently, the technique for harvesting, processing/ preparation, and delivery of fat has been refined, and longterm corrective results have been documented.1 Having said that, it is important to note that the predictability of this procedure depends on many factors, making it challenging for novice practitioners to successfully achieve desired outcomes.

Collagen

Collagen is one of the most important components of the dermis, and so, quite naturally, was developed for cosmetic applications. Injectable bovine collagen was the first dermal filler to be granted US FDA clearance more than 25 years ago. There are several sources of injectable collagen available. (See Table 1)

Although skin testing is required for some of the earlier established bovine-derived products, the newer injectable collagens do not require skin allergy testing. The recently introduced porcine-derived Evolence™, with an innovative cross-linking technology, has been shown to produce longer lasting results than Zyplast® for the correction of nasolabial folds.2 Collagen-based products enjoy an impressive long-term safety profile and, as such, will remain one of the more popular choices for dermal augmentation.

Collagen Sources

Type

Trade Names (Manufacturer)

Human Autologous Isolagen™ Therapy* (Isolagen)
Allogenic Cymetra® (LifeCell)
Cosmoderm® (Inamed)
Cosmoplast® (Inamed)
Alloderm® (LifeCell)
Bovine Zyderm® (Inamed)
Zyplast® (Inamed)
Porcine Evolence® (ColBar LifeScience)
Table 1: Sources of injectable collagen.
*Not approved by the US FDA

Hyaluronic Acid

Hyaluronic acid (HA) is a naturally occurring linear polysaccharide that is a component of all connective tissues. Because of its uniform structure throughout all living species, adverse immune reactions are rare. HA has hydrophilic properties, allowing it to attract and attach to water molecules. There are several families of popular HA injectables. (See Table 2)

Manufacturer

Trade Name

Derivation

Q-Med Restylane® NAD
Restylane® Fine Lines
Restylane® SubQ
Perlane®
Inamed Hylaform® Plus AD
Hylaform® Fine Line
Juvederm™ Ultra Plus NAD
Juvederm™ Ultra
Teoxane Teosyal® Kiss
Teosyal® Ultra Deep
Galderma/ Anika Elevess™ NAD
Table 2: Families of popular HA injectables. NAD = non-animal derived; AD = animal derived.

The duration of benefit following therapy with different HA fillers has not been rigorously studied. Although all products contain essentially the same HA molecule, the differences between the formulations relate to the quantity/ concentration of HA, the degree of crosslinking, and the amount of proteins incorporated, which affect flow characteristics and the target placement within the dermal-subcutaneous continuum.3,4 Recently, a new HA product has been approved by the US FDA for soft tissue augmentation, Elevess™ (Anika Therapeutics). This novel formulation includes a high concentration of HA combined with lidocaine, which can provide patients with a more comfortable procedural experience.

The versatility of HA products expands the physician's options when selecting an implant for each unique application (dermal, subdermal, subcutaneous or supraperiosteal injections). This versatility, combined with the low risk of immune reactions, makes HA products the cornerstone of injectable fillers.

Calcium Hydroxylapatite

Calcium hydroxylapatite (CaHA), the major mineral constituent of bone, has been used for more than a decade in dentistry and reconstructive surgery. Its safety record in these disciplines is well established. Recently, a product containing microscopic CaHA particles suspended in a polysaccharide gel (Radiesse®, BioForm Medical) has been successfully used for aesthetic soft tissue augmentation.5 When injected, the small particles of CaHA act as a scaffold for collagen to grow. Because there are no animal-based ingredients contained in the product, skin testing is not required. Over time, CaHA particles are slowly dissolved into calcium and phosphate ions through normal metabolic processes. Current studies indicate that some degree of correction persists for up to 18 months.6 It is important to note that CaHA is radio opaque and can be visible on regular X-Rays.

Poly-L-Lactic Acid

Poly-L-lactic acid (PLLA) (Sculptra™, Sanofi-Aventis) is not a classic filler, but rather, a stimulator. PLLA has been safely used for over 4 decades as suture material. It is a nontoxic, immunologically inactive, synthetic biodegradable lactic acid polymer. Unlike other products discussed in this review, Sculptra™ is reconstituted with sterile water prior to injection. The mixture is injected into the deep dermis or subcutaneous space with the tunneling or threading technique. It is important to distribute the product evenly to minimize the possibility of granuloma formations. Patients usually require three monthly treatments to achieve the desired results. With each treatment, there is stimulation of neocollagenesis secondary to small PLLA particles. It is important to note that the initial studies demonstrate an increase in skin thickness as early as 6 weeks after injection.7 The duration of the desired effects can last up to 96 weeks, making Sculptra™ a unique option to consider, as well as providing extended results for the patient.

Silicone

Silicone oil, derived from silica and composed of purified polydimethylsiloxane, has been used for facial augmentation and scar revision for decades. The recent introduction of Silikon® 1000 (Alcon Laboratories) has revived the use of this controversial filler. A microdroplet technique is used to inject silicone into the dermalsubcutaneous junction. Overcorrection is avoided and repeat treatments at intervals of 4–6 weeks are advisable. Complications in the past, such as granulomas, were primarily due to large volume injections or adulteration of the silicone used. Because injected silicone provides permanency, it does not require skin testing and will not support bacterial growth. Its cost, relative to other available dermal fillers on the market, make it an attractive option, however, more research is needed to fully establish its place in the aesthetic arena.

Polymethylmethacrylate

Polymethylmethacrylate (PMMA) microspheres (Artecoll®, Artefill®, Artesense™, Artes Medical) is a permanent filler and stimulator of neo collagenesis, where the PMMA particles are suspended in a collagen vehicle. Following the injection, the collagen is quickly degraded, leaving the PMMA beads indefinitely; the subsequent collagen reaction around the particles creates volume. Unlike temporary fillers, the immediate filling effect disappears rather quickly and, over time, gradual, but long-lasting correction is established. Although granulomas have been reported, with the use of proper technique (injection at the dermal subcutaneous junction using threading or tunneling methods) and applying a series of injections at appropriate sites, PMMA fillers can provide excellent long-term correction.8

Adverse Effects

Complications arising from soft tissue augmentation can be attributed to several factors: the patient, the physician, and product characteristics.9 Patient suitability and appropriate product selection are paramount in obtaining the desired results. However, even if these criteria are satisfied, complications can arise.

The most common early side-effects include bleeding (bruising and hematomas), pain, swelling, and erythema. To reduce the incidence and the severity of these complications, any substance that can impede blood clotting (e.g., acetylsalicylic acid, nonsteroidal antiinflammatory drugs, and excessive alcohol consumption) should be discontinued for an appropriate length of time prior to receiving treatment unless otherwise recommended by a physician. In addition, appropriate topical, as well as local/ regional anesthesia, and cold compresses can be used to relieve mild symptoms. Rare complications, such as skin necrosis and blindness, require rapid diagnosis and immediate intervention. Delayed complications include chronic inflammation, late allergic reactions, nodules, granulomas, discoloration, migration, and hypertrophic scarring. Although some of these adverse reactions cannot be predicted, early detection and initiation of appropriate therapy can help to minimize patient discomfort, severity of side-effects, and prevent the onset of sequelae.

Conclusion

The ever-expanding array of products for soft tissue augmentation is of real benefit for patients and physicians. From the patients’ perspective, expectation of results, safety, and product durability are of primary concern. Physicians, on the other hand, can combine their knowledge of the anatomy and the ageing process to assess patient suitability, and determine the choice of product that will ultimately provide the results that each individual patient expects and deserves. As always, safety is of paramount importance, especially when physicians are dealing with the vulnerabilities of their patients.

References

  1. Butterwick KJ, Nootheti PK, Hsu JW, et al. Autologous fat transfer: an in-depth look at varying concepts and techniques. Facial Plast Surg Clin North Am 15(1):99-111 (2007 Feb).
  2. Monstrey SJ, Pitaru S, Hamdi M, et al. A two-stage phase I trial of Evolence30 collagen for soft-tissue contour correction. Plast Reconstr Surg 120(1):303-11 (2007 Jul).
  3. Lupo MP. Hyaluronic acid fillers in facial rejuvenation. Semin Cutan Med Surg 25(3):122-6 (2006 Sep).
  4. Lowe NJ, Grover R. Injectable hyaluronic acid implant for malar and mental enhancement. Dermatol Surg 32(7):881-5 (2006 Jul).
  5. Alam M, Yoo SS. Technique for calcium hydroxylapatite injection for correction of nasolabial fold depressions. J Am Acad Dermatol 56(2):285-9 (2007 Feb).
  6. Silvers SL, Eviatar JA, Echavez MI, et al. Prospective, open-label, 18-month trial of calcium hydroxylapatite (Radiesse®) for facial soft-tissue augmentation in patients with human immunodeficiency virus-associated lipoatrophy: one-year durability. Plast Reconstr Surg 118(3 Suppl):34S-45S (2006 Sep).

  1. Dermatological Management of Human Immunodeficiency Virus (HIV)
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  3. Update on Drugs and Drug News - October 2007